Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient

Masuda, S Uemoto, S Hashida, T Inomata, Y Tanaka, K Inui, K

S. Masuda et al., Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient, CLIN PHARM, 68(1), 2000, pp. 98

18

INGLESE

Article

Pharmacology,"Pharmacology & Toxicology

CLINICAL PHARMACOLOGY & THERAPEUTICS

0009-9236 → ACNP

68

1

2000

ISI

0009-9236(200007)68:1<98:EOIPOD>2.0.ZU;2-S

We have examined whether the expression levels of the intestinal absorptive barriers, MDR1 gene product P-glycoprotein and cytochrome P450 IIIA4 (CYP3 A4), correlate with the trough levels of orally administered tacrolimus in a recipient of small bowel transplant for 4 months. By using a competitive polymerase chain reaction, the expression of MDR1 messenger RNA (mRNA) and CYP3A4 mRNA by intestinal cells in a part of the mucosa biopsy specimen was evaluated. The average mRNA expression levels of MDR1 and CYP3A4 were 8.6 and 39.6 amol/mu g total RNA, respectively. Both the MDR1 and CYP3A4 mRNA l evels changed markedly throughout this period. The tacrolimus concentration /dose ratio correlated well with the mRNA expression level of MDR1, but not CYP3A4, These results suggested that intestinal P-glycoprotein rather than CYP3A4 is a good probe to predict the intraindividual variation in the tac rolimus pharmacokinetics during immunosuppressant therapy after small bowel transplantation.